The overall objective of this research program is to test in the baboon (Papio sp.) selected hypotheses concerning the mechanism of action of the established human risk factors for the atherosclerotic diseases, the interactions among these risk factors, and the potential role of suspected risk factors under controlled experimental conditions. Because it is well established as a major factor in human and experimental atherosclerosis and because it is effective in the baboon, diet-induced hyperlipidemia in the human range (200-300 mg/dl serum cholesterol) is used as a basic manipulation in most experiments. Several experiments are directed at the control mechanisms determining the individual's response to diet, particularly genetic constitution, infant nutrition, and intestinal microflora. Risk factors being studied for their modulatng effect on diet-induced atherogenesis include obesity, hypertension, cigarette smoking, and behavioral type. The genetic studies are combined with experiments testing the effects of various infant feeding regimens on long-term response to diet and susceptibility to atherosclerosis. Initially, they are designed to develop strains of baboons with enhanced characters related to atherosclerosis, and then to search for monogenic variants. Core laboratories supporting these experiments include those specializing in lipid biochemistry behavioral observation and manipulation, pathology and morphometry, biometry and data management, veterinary care and program administration.